9-Arylmethyl-substituted purines (including guanines) have been reported as PNP inhibitors in EP-A-0,178,178 substantially corresponding to U.S. Pat. No. 4,772,606. 9-arylmethyl-substituted purines (including guanines), in which the aryl ring contains phosphonic acid groups, have also been reported as PNP inhibitors in EP-A-0,465,297 WO-A-92/05180. Modified purines, namely 9-deazapurines, have also been reported as PNP inhibitors in U.S. Pat. No. 4,985,434; U.S. Pat. No. 5,008,265; U.S. Pat. No. 4,985,433; U.S. Pat. No. 5,236,926; U.S. Pat. No. 5,236,926 and U.S. Pat. No. 5,008,270.
PNP inhibitory data cited in Drugs of the Future, 13, 654 (1988), Agents and Actions, 21, 253 (1987), Proc Natl Acad Sci USA, 88, 11540 (1991) and U.S. 90/01021 indicate that modifications to the guanine base markedly alter the PNP inhibitory ability of such compounds. Also, modifications to the aryl ring of the 9-deaza (9-arylmethyl) purines can markedly alter PNP inhibitory activity. Namely replacement of a pyridine ring with piperidine greatly reduces activity as illustrated in IL Farmaco, 48 (2), 297 (1993).